Aspirin, marketed by Bayer AG (Germany) in last-century, is a famous anti-inflammatory, antipyretic, and analgesic agent. Although the commonly used anti-inflammatory agents such as aspirin have favorable anti-inflammatory, antipyretic, and analgesic effects, they exhibit apparent toxicity on gastrointestinal tracts and kidneys. The toxic and side effects of aspirin are due to that aspirin is not a specific COX-2 inhibiting agent.
Studies have proven that, endosomatic cyclooxygenases have two kinds of subtypes: COX-1 and COX-2. COX-1 is present in normal tissue cells and plays an important role in protecting mucous cells of gastrointestinal tracts and maintaining the normal functions of blood platelets and kidneys. COX-2 is mainly present in inflammation tissues. COX-2 can promote the production of various prostaglandins by inflammatory cells, induce inflammatory response, and thus cause pain and pyrexia and the like symptoms. Recent studies indicate that the activity of COX-2 in tumour tissues is higher than that in normal tissues.
The results of amino acid sequencing and X-ray diffraction on structures of cyclooxygenases indicate that COX-1 and COX-2 have approximately 60% identity in their amino acid sequences and the main catalytic groups in their catalysis active centers are substantially similar, with only small differences, such as COX-1 having isoleucine-523, while COX-2 has valine-523. In addition, the amino acid residues at the entrance of the active center of COX-1 are also different from those of COX-2.
Aspirin can not distinguish the structural differences between COX-1 and COX-2. Aspirin can acylate serine-530 of both COX-1 and COX-2. As a result, the actions of both COX-1 and COX-2 are inhibited. Therefore, the anti-inflammatory agents, for example, the nonspecific COX inhibiting agents such as Aspirin, inhibit not only the production of prostaglandins which participate in inflammatory responses, but also the syntheses of prostaglandins which bring normal physiological effects, and result in toxic and side effects.